Impact of Consumption of Beta-glucans on the Intestinal Microbiota and Glucose and Lipid Metabolism

• ClinicalTrials.gov Identifier: NCT02041104
• Recruitment Status: Completed
• First Posted: January 20, 2014
• Results First Posted: June 3, 2019
• Last Update Posted: June 3, 2019
• Sponsor: Mlinotest Zivilska Industrija d.d.
• Collaborators: University of Ljubljana; University Medical Centre Ljubljana
• Information provided by (Responsible Party): Mlinotest Zivilska Industrija d.d.

Study Description

Brief Summary:

The purpose of this study is to investigate if daily consumption of barley beta-glucans effect lipid and glucose metabolism and alter intestinal microbiota composition in participants with metabolic syndrome or with high risk for metabolic syndrome development. It is assumed that 4-week intervention with beta-glucans will improve some clinical signs of metabolic syndrome and alter composition of intestinal microbiota. Variation in microbiota composition will be investigated with emphasis on Bacteroidetes and Firmicutes ratio. Furthermore it is presupposed that consumption of beta-glucans will stimulate growth of beneficial intestinal bacteria from genus Lactobacillus and Bifidobacteria and consequently effect production of short chain fatty acids in population with metabolic syndrome. Moreover it is presupposed that 4-week consumption of beta-glucans will have influence on glucose metabolism and will consequently improve insulin resistance within people with metabolic syndrome or high risk for metabolic syndrome development. It is assumed that 4-week consumption of beta-glucans will improve specific plasma lipid content in population with metabolic syndrome.

Condition or disease	Intervention/treatment	Phase
Metabolic Syndrome; Dyslipidemia; Obesity, Abdominal; Hyperglycemia; Hypertension	Dietary Supplement: Bread with added beta-glucans; Dietary Supplement: Placebo Comparator: Bread without added beta-glucans	Not Applicable

Detailed Description:

In study it will be investigated whether daily consumption of barley beta-glucans integrated in bread product effects lipid and glucose metabolism and alter the composition of intestinal microbiota in a population with metabolic syndrome or with high risk for metabolic syndrome development. 70 participants with metabolic syndrome will be enrolled in study. Participants will daily consume 200 g of bread with high amount of beta-glucans.

Hypothesis:

1. 4- week consumption of beta-glucans alters composition of intestinal microbiota and changes ratio of bacteria from phylum Bacteroidetes and Firmicutes. Furthermore consumption of beta-glucans stimulates growth of beneficial intestinal bacteria from genus Lactobacillus and Bifidobacteria and consequently effects production of short chain fatty acids in population with metabolic syndrome.
2. 4- week consumption of beta-glucans has influence on glucose metabolism and consequently improves insulin resistance within people with metabolic syndrome.
3. 4 - week consumption of beta-glucans improves specific plasma lipid content in population with metabolic syndrome.

Study will be designed as double blind, randomised, placebo controlled clinical trial and performed regarding to CONSORT 2010 recommendations for randomised clinical trials. Patient enrollment will be performed in several community health centres in Slovenia in association with family medicine doctors. Appropriate patients with metabolic syndrome or with high risk for metabolic development will be suggested to participate in clinical trial. Candidates will be suggested to participate in a two month study. If there will not be recruited enough participants for two month study they will be suggested for participation in one month study. Candidates interested in participating in study will be informed about study design and terms and conditions of study by main investigator.

Study will be performed after successful recruitment of first 20 or more participants. Study will be performed three times, so that 70 participants will be recruited in complete study. Participants will consume bread with high beta-glucans content (around 3, 4 g beta-glucans per 100 g of bread) during 8 or 4 week period. Before beginning of study participants will have two week washout period without consuming any pre- and pro-biotics. They will remain their usual eating habits during study period except taking any antibiotics or pre- and pro-biotic. Participants will give blood and stool samples a day before intervention with barley beta-glucans. Blood sampling will involve oral glucose test for insulin resistance determination and sampling for specific lipid content determination. They will also have option to give a blood sample for genetic investigation of genes associated with lipid metabolism (apoE). Blood and stool sampling will be repeated day after intervention period. The same parameters as before intervention period except genetic analysis will be investigated. 72-hour dietary recall will be performed during intervention period individually to evaluate daily nutrient and energetic input of each participant.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Impact of Consumption of Beta-glucans on the Intestinal Microbiota and Glucose and Lipid Metabolism in a Population With Metabolic Syndrome
• Study Start Date: February 2014
• Actual Primary Completion Date: April 2018
• Actual Study Completion Date: April 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Bread with added beta-glucans; Experimental food is bread with high amount of barley beta-glucans. Experimental bread contains approximately 3,4 % (w/w) beta-glucans. Participants will consume 6 g of beta-glucans daily (approximately 200 g of bread per day). Beta-glucans are natural polysaccharides found in grain endosperm and are mostly represented in oat and barley. Beta-glucans are linear homopolymers of D- glycopyranosyl residues with mixed linkage (1-4, 1-3)-β-D-glucans. Their molecular structure enable beta-glucans their functional action that mostly depends of their viscosity and solubility (1). Testing bread has integrated flour with high amount of barley beta-glucans (ReducholTM). Beta-glucans are concentrated in flour up to 15 % with dry milling, sieving and air classification of barley flour.	Dietary Supplement: Bread with added beta-glucans; Participants will daily consume bread with high content of beta-glucans. They will approximately consume 6 g beta-glucans per day in 200 g of bread. Intervention period will be 4 weeks. Meanwhile the participants will remain their usual eating habits except consuming any pro- or pre-biotics
Placebo Comparator: Bread without added beta-glucans; Placebo bread without added barley beta-glucans in testing product.	Dietary Supplement: Placebo Comparator: Bread without added beta-glucans; Participants will daily consume placebo bread without any added beta-glucans (approximately 200 g per day). Intervention period will be 4 weeks. Meanwhile the participants will remain their usual eating habits except consuming any pro- or pre-biotics.

Outcome Measures

Primary Outcome Measures :

1. Total Cholesterol Levels [ Time Frame: Baseline outcome measurement ]
   Before the intervention, total cholesterol levels were determined.
2. HDL-cholesterol Levels [ Time Frame: Baseline measurement ]
   HDL-cholesterol levels were determined before diet intervention.
3. LDL-cholesterol Levels [ Time Frame: Baseline measurement ]
   LDL-cholesterol levels were determined before intervention
4. Determination of Composition of Intestinal Microbiota From Fecal Samples [ Time Frame: Outcome measurement at baseline ]
   Fecal sampling for microbiologic analysis of microbiota composition: Composition of intestinal microbiota will be determined with a combination of two molecular techniques denaturating gradient gel electrophoresis (DGGE) and quantitative real time PCR (RT-PCR).
5. Oral Glucose Tolerance Test (OGTT) for Insulin Resistance Determination (Outcome Measures of Plasma Insulin Concentrations) [ Time Frame: OGTT measurements performed before dietary intervention ]

   Pharmacokinetic outcome measures: Determination of insulin resistance with OGTT testing. Before and after oral consumption of 75 g of glucose, plasma insulin concentrations were measured at following times:

   0 min - before oral consumption of 75 g glucose 30 min, 60 min and 120 min - after oral consumption of 75 g glucose

6. Oral Glucose Tolerance Test (OGTT) for Insulin Resistance Determination (Outcome Measures of Plasma Glucose Concentrations) [ Time Frame: Outcome OGTT measurements performed before dietary intervention ]

   Pharmacokinetic outcome measures: Determination of insulin resistance with OGTT testing. Before and after oral consumption of 75 g of glucose, plasma glucose concentrations were measured at following times:

   0 min - before oral consumption of 75 g glucose 30 min, 60 min and 120 min - after oral consumption of 75 g glucose

7. Systolic and Diastolic Blood Pressure [ Time Frame: Outcome measurement at baseline. ]
   Before the intervention, systolic and diastolic blood pressure were measured. Measurement was performed to obtain parameters for metabolic syndrome definition. Measurements after dietary intervention weren`t performed.
8. Determination of Concentration of Short Chain Fatty Acids (SCFA) Present in Fecal Samples [ Time Frame: Outcome measurement at baseline ]
   Fecal sampling for SCFA determination: Content of specific SCFA (butyric acid, acetic acid and propionic acid) will be determined in fecal samples using Gas Chromatography.
9. Triglyceride Levels [ Time Frame: Outcome measure at baseline. ]
   Before the diet intervention, triglyceride levels were measured in test (consuming bread with added beta glucans) and in control group (consuming bread without added beta glucans).

Secondary Outcome Measures :

1. Determination of Composition of Intestinal Microbiota From Fecal Samples [ Time Frame: Outcome measurement after 4-week dietary intervention ]
   Fecal sampling for microbiologic analysis of microbiota composition: Composition of intestinal microbiota will be determined with a combination of two molecular techniques denaturating gradient gel electrophoresis (DGGE) and quantitative real time PCR (RT-PCR).
2. Determination of Concentration of Short Chain Fatty Acids (SCFA) Present in Fecal Samples [ Time Frame: Outcome measurement after 4-week dietary intervention ]
   Fecal sampling for SCFA determination: Content of specific SCFA (butyric acid, acetic acid and propionic acid) will be determined in fecal samples using Gas Chromatography.
3. LDL-cholesterol Levels [ Time Frame: Outcome measurement after 4-week dietary intervention ]
   LDL-cholesterol levels were determined after intervention
4. HDL-cholesterol Levels [ Time Frame: Outcome measurement after 4-week dietary intervention ]
   HDL-cholesterol levels were determined after diet intervention.
5. Triglyceride Levels [ Time Frame: Outcome measure after 4-week dietary intervention. ]
   After the diet intervention, triglyceride levels were measured in test (consuming bread with added beta glucans) and in control group (consuming bread without added beta glucans).
6. Total Cholesterol Levels [ Time Frame: Outcome measurement after 4-week dietary intervention ]
   After the intervention, total cholesterol levels were determined.
7. Oral Glucose Tolerance Test (OGTT) for Insulin Resistance Determination (Outcome Measures of Plasma Glucose Concentrations) [ Time Frame: Outcome OGTT measurements performed after 4-week dietary intervention ]

   Pharmacokinetic outcome measures: Determination of insulin resistance with OGTT testing. Before and after oral consumption of 75 g of glucose, plasma glucose concentration measurements were performed at following times:

   0 min - before oral consumption of 75 g glucose 30 min, 60 min and 120 min - after oral consumption of 75 g glucose

8. Oral Glucose Tolerance Test (OGTT) for Insulin Resistance Determination (Outcome Measures of Plasma Insulin Concentrations) [ Time Frame: Outcome OGTT measurements performed after 4-week dietary intervention ]

   Pharmacokinetic outcome measures: Determination of insulin resistance with OGTT testing. Before and after oral consumption of 75 g of glucose, plasma insulin concentration measurements were performed at following times:

   0 min - before oral consumption of 75 g glucose 30 min, 60 min and 120 min - after oral consumption of 75 g glucose

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria are parameters used for metabolic syndrome determination according to International Diabetes Federation (IDF) consensus worldwide definition of Metabolic Syndrome:

Participant must have central obesity: defined as waist circumference ≥ 80 cm for European woman and ≥ 94 cm for European men. Beside central obesity candidates participating in this study must have total cholesterol concentration ≥ 5 mmol/l before entering the study.

Plus any two of the following four factors:

• HDL-cholesterol content: man ≤ 1,03 mmol/, women ≤ 1,23 mmol/l
• Triglycerides content ≥ 1,7 mmol/l
• Fasting blood glucose ≥ 5,6 mmol/l
• Hypertension: systolic blood pressure ≥ 130 mm Hg and diastolic blood pressure ≥ 85 mm Hg

If participant will have diagnosed metabolic syndrome and meet age criteria will be included in study.

Exclusion Criteria:

• Diabetes type II
• Thyroid disorder
• Kidney disorder
• Antibiotic treatment

Contacts and Locations

Locations

Slovenia

Community Health Center Ajdovscina

Ajdovscina, Slovenia, 5270

Community Healt Center Ljubljana

Ljubljana, Slovenia, 1000

Community Health Center Franca Amrozica Postojna

Postojna, Slovenia, 6230

Sponsors and Collaborators

Mlinotest Zivilska Industrija d.d.

University of Ljubljana

University Medical Centre Ljubljana

Investigators

• Principal Investigator: Ana Velikonja, PhD student; Mlinotest d.d. Zivilska Industrija
• Study Director: Rok Orel, M.D., D.Sc.; University Medical Centre Ljubljana
• Study Director: Gorazd Avgustin, UP; University of Ljubljana

  Study Documents (Full-Text)

Documents provided by Mlinotest Zivilska Industrija d.d.:

Statistical Analysis Plan  [PDF] May 15, 2018

Study Protocol  [PDF] August 22, 2013

More Information

Additional Information:

International Diabetes Federation (IDF) consensus worldwide definition of Metabolic Syndrome 

Publications:

(1) Izydorczyk MS,Dexter JE. Barley beta-glucans and arabinoxylans: Molecular structure, physicochemical properties, and uses in food products-a Review. Food Research International 41: 850-868, 2008

• Responsible Party: Mlinotest Zivilska Industrija d.d.
• ClinicalTrials.gov Identifier: NCT02041104 History of Changes
• Other Study ID Numbers: MLINOTEST/618-001
• First Posted: January 20, 2014
• Results First Posted: June 3, 2019
• Last Update Posted: June 3, 2019
• Last Verified: February 2019

Keywords provided by Mlinotest Zivilska Industrija d.d.:

Metabolic syndrome; 4 -week intervention; Randomised placebo controlled parallel study; Beta-glucans; Abdominal fat; Dyslipidemia; Insulin resistance; Hypertension; Gut Microbiota Composition; Oral Glucose Tolerance Test; Lipid Profile; Real-Time Polymerase Chain Reaction; Denaturating Gradient Gel Electrophoresis

Additional relevant MeSH terms:

Hypertension; Metabolic Syndrome; Dyslipidemias; Hyperglycemia; Obesity, Abdominal; Syndrome; Disease; Pathologic Processes; Vascular Diseases; Cardiovascular Diseases; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Lipid Metabolism Disorders; Obesity; Overnutrition; Nutrition Disorders